Cargando…

Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia

Myeloid-derived suppressor cells (MDSC) are a group of heterogeneous immature myeloid cells and display immunosuppressive function. In this study, MDSC populations were evaluated in acquired aplastic anemia (AA) (n=65) in which aberrant immune mechanisms contributed to bone marrow destruction. Our d...

Descripción completa

Detalles Bibliográficos
Autores principales: Dong, Peiyuan, Chen, Lingyun, Wu, Hongfei, Huo, Jiali, Jiang, Zhongxing, Shao, Yingqi, Ren, Xiang, Huang, Jinbo, Li, Xingxin, Wang, Min, Nie, Neng, Zhang, Jing, Jin, Peng, Zheng, Yizhou, Ge, Meili
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713570/
https://www.ncbi.nlm.nih.gov/pubmed/35734923
http://dx.doi.org/10.3324/haematol.2021.280292
_version_ 1784842042958938112
author Dong, Peiyuan
Chen, Lingyun
Wu, Hongfei
Huo, Jiali
Jiang, Zhongxing
Shao, Yingqi
Ren, Xiang
Huang, Jinbo
Li, Xingxin
Wang, Min
Nie, Neng
Zhang, Jing
Jin, Peng
Zheng, Yizhou
Ge, Meili
author_facet Dong, Peiyuan
Chen, Lingyun
Wu, Hongfei
Huo, Jiali
Jiang, Zhongxing
Shao, Yingqi
Ren, Xiang
Huang, Jinbo
Li, Xingxin
Wang, Min
Nie, Neng
Zhang, Jing
Jin, Peng
Zheng, Yizhou
Ge, Meili
author_sort Dong, Peiyuan
collection PubMed
description Myeloid-derived suppressor cells (MDSC) are a group of heterogeneous immature myeloid cells and display immunosuppressive function. In this study, MDSC populations were evaluated in acquired aplastic anemia (AA) (n=65) in which aberrant immune mechanisms contributed to bone marrow destruction. Our data demonstrate that both the proportion and immunosuppressive function of MDSC are impaired in AA patients. Decreased percentage of MDSC, especially monocytic MDSC, in the blood of AA patients (n=15) is positively correlated with the frequency of T-regulatory cells, bone marrow level of WT1 and decreased plasma level of arginase-1. RNA sequencing analyses reveal that multiple pathways including DNA damage, interleukin 4, apoptosis, and Jak kinase singnal transducer and activator of transcription are upregulated, whereas transcription, IL-6, IL-18, glycolysis, transforming growth factor and reactive oxygen species are downregulated in MDSC of AA (n=4), compared with that of healthy donors (n=3). These data suggest that AA MDSC are defective. Administration of rapamycin significantly increases the absolute number of MDSC and levels of intracellular enzymes, including arginase-1 and inducible nitric-oxide synthase. Moreover, rapamycin inhibits MDSC from differentiating into mature myeloid cells. These findings reveal that impaired MDSC are involved in the immunopathogenesis of AA. Pharmacologically targeting of MDSC by rapamycin might provide a promising therapeutic strategy for AA.
format Online
Article
Text
id pubmed-9713570
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Fondazione Ferrata Storti
record_format MEDLINE/PubMed
spelling pubmed-97135702022-12-12 Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia Dong, Peiyuan Chen, Lingyun Wu, Hongfei Huo, Jiali Jiang, Zhongxing Shao, Yingqi Ren, Xiang Huang, Jinbo Li, Xingxin Wang, Min Nie, Neng Zhang, Jing Jin, Peng Zheng, Yizhou Ge, Meili Haematologica Article - Bone Marrow Failure Myeloid-derived suppressor cells (MDSC) are a group of heterogeneous immature myeloid cells and display immunosuppressive function. In this study, MDSC populations were evaluated in acquired aplastic anemia (AA) (n=65) in which aberrant immune mechanisms contributed to bone marrow destruction. Our data demonstrate that both the proportion and immunosuppressive function of MDSC are impaired in AA patients. Decreased percentage of MDSC, especially monocytic MDSC, in the blood of AA patients (n=15) is positively correlated with the frequency of T-regulatory cells, bone marrow level of WT1 and decreased plasma level of arginase-1. RNA sequencing analyses reveal that multiple pathways including DNA damage, interleukin 4, apoptosis, and Jak kinase singnal transducer and activator of transcription are upregulated, whereas transcription, IL-6, IL-18, glycolysis, transforming growth factor and reactive oxygen species are downregulated in MDSC of AA (n=4), compared with that of healthy donors (n=3). These data suggest that AA MDSC are defective. Administration of rapamycin significantly increases the absolute number of MDSC and levels of intracellular enzymes, including arginase-1 and inducible nitric-oxide synthase. Moreover, rapamycin inhibits MDSC from differentiating into mature myeloid cells. These findings reveal that impaired MDSC are involved in the immunopathogenesis of AA. Pharmacologically targeting of MDSC by rapamycin might provide a promising therapeutic strategy for AA. Fondazione Ferrata Storti 2022-06-23 /pmc/articles/PMC9713570/ /pubmed/35734923 http://dx.doi.org/10.3324/haematol.2021.280292 Text en Copyright© 2022 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article - Bone Marrow Failure
Dong, Peiyuan
Chen, Lingyun
Wu, Hongfei
Huo, Jiali
Jiang, Zhongxing
Shao, Yingqi
Ren, Xiang
Huang, Jinbo
Li, Xingxin
Wang, Min
Nie, Neng
Zhang, Jing
Jin, Peng
Zheng, Yizhou
Ge, Meili
Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia
title Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia
title_full Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia
title_fullStr Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia
title_full_unstemmed Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia
title_short Impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia
title_sort impaired immunosuppressive role of myeloid-derived suppressor cells in acquired aplastic anemia
topic Article - Bone Marrow Failure
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9713570/
https://www.ncbi.nlm.nih.gov/pubmed/35734923
http://dx.doi.org/10.3324/haematol.2021.280292
work_keys_str_mv AT dongpeiyuan impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT chenlingyun impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT wuhongfei impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT huojiali impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT jiangzhongxing impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT shaoyingqi impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT renxiang impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT huangjinbo impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT lixingxin impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT wangmin impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT nieneng impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT zhangjing impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT jinpeng impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT zhengyizhou impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia
AT gemeili impairedimmunosuppressiveroleofmyeloidderivedsuppressorcellsinacquiredaplasticanemia